The pathology and etiology of infectious diseases

Introduction

Uew branches of medical science can be said to have received, witliin the last twenty-five years, greater attention, and to have developed more largely within a comparatively short period, than the knowledge of the nature of infectious diseases. Not only have many disorders, belonging to this class and for a long time suspected as belonging to this group, become well understood in their nature, their mode of origin and spread, but others, not previously suspected to be communicable diseases at all, have been shown to appertain to this class. To quote for each of these one instance : typhoid fever, though for a long time assumed to be a communicable disorder spreading from the sick to the healthy by the evacuations, had not, prior to the researches of Budd, Snow, Simon, Buchanan and others, been proved to be of this character, and though some authorities, like Murchison, pleaded for the possibility of a spontaneous origin, the weight of evidence was in favour of its being a specific disease, which, like all specific diseases, can only arise from a previous specific disorder of the same kind. By the researches of more modern investigators, notably Buchanan, Ballard, and Thorne Thorne, its mode of spread has become well understood, and by their investigations its nature — viz. that of a specific communicable disease — been definitely settled. As examples of diseases not previously suspected to belong to this group but now known to be so, we may quote tetanus, and epidemic or croupous pneumonia. Of both these diseases recent research has shown that they are of an infectious character, that in both there exists a specific virus which, finding entrance into a healthy individual, is capable of setting up the disorder. These examples we could easily multiply. Nay more, we could show, on the one hand, that as regards a number of disorders for whose specific nature there existed until quite recently very slender evidence, there are now definite and exact experimental grounds for asserting their specific nature, e.g. anthrax, tuberculosis, septicaemia, and erysipelas ; on the other hand, by ascertaining the exact nature of some of these disorders, others formerly not distinguished from them have been shown to have a separate existence and to be different from them in their pathology, symptoms, course, and causation. Thus, for instance, malignant anthrax has been shown to be a perfectly separate disorder from symptomatic anthrax ; wxxfisorters’ disease (malignant pustule) to be a separate disease from some forms of ragsorters’ disease ; tuberculosis to be different from other chronic lung diseases, to which it bears a distant pathological semblance.

These results have been achieved by the isolation and study of the essence of these diseases — the contcigium, which was showrn to be a living microphyte,1 contagium vivum, differing as regards morphology and biology in the different diseases to which it gives rise. It is no doubt an interesting study to trace the history and the development of the theory of the contagium vivum ; but at the present day such a study is chiefly of an historical interest, and not an

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integral part of the present work. It is interesting to go back to the ‘ when the basis of 1 discussion as to whether infectious ***** can. arise do novo was evidence such as the existence of epidemics aiismg imported from outside (small-pox, the plague, dx *0. ””udl that the isolation of the patient, and destructor .of:

a patient, puts a stop to, or prevents the spread of that disorder o ^ ^ similarity of tlie specific nature and spread of infect aled

specific nature of fermentations, such as those spe, =>^ “7^ by the earlier labours of M. Pasteur, was insisted on. A .t present that infectious diseases owe their origin to specific .Ye’1;,^“t^ceptibie.

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microscopical, cultural, and animal experiments demons rate the sp matevies mor hi-, more than that ;,m cases where the '

tubercle bacilli, is enabled to settle the point without difficulty. The sa

holds crood in certain surgical cases, where the diagnosis of tuberculosis o i • ° kppq is onlv possible after the demonstration of the tubercle bacilli..

sheep and cattle, and wool and hide ^sorter,

the exact and reliable diagnosis of malignant anthrax is furnished by the

demonstration of the bacillus anthracis by the microscope, by culture, and by demonstration o ^ suspected cases of cholera, when the clinical

aspect is not sufficiently characteristic, the demonstration of the choleraic comma bacilli in the evacuations, or in the contents of the intestines, furnishesan important piece of evidence. In cases of suspected rabies, the expenml ™thod discovered by M. Pasteur-viz. that the spinal marrow of

Id anmi mal inoculated under the dura mater of a rabbit produces hydrosuch ari itive pr00f. The differential diagnosis between tuber-

Sosis an actinomycosis in cattle, possible by the microscopic test, furnishes atTer not less important illustration. The study of micro-organisms coni- a un qnprifie diseases — i.e. the contagicc, their nature, habits, am

^within an infecfed individual, the manner in

Which they leave and in which they enter the human and animal organism, the nature of the changes which they induce m the material in which they ‘row and multiply, be that material the human or animal organism, oi organic matter outside these-all this is now well understood.

The micro-organisms or microbes 1 that interest us belong to three distinct

croups : (1) bacteria, (2) fungi, (3) monadinse. The first are those which as t Microbe (fJUKpis, small, iBios, life) is the term also generally applied to these microscopic organisms.

regards infectious diseases hold the most prominent place, owing to their general and very wide distribution, and because most of the infectious disorders hitherto analysed owe their origin to one or another species of these microphytes; the second or fungi have, so far as research has hitherto gone, a more limited distribution as disease-producers ; and the third group, or monadinae and allied organisms, belonging to the animal kingdom, are at present only imperfectly investigated, although, as will be shown, they produce some well-marked disorders in man and animals.

Section A.

Chapter I Characters Of Bacteria

Bacteria are microscopic organisms which contain no chlorophyll, which possess an investment of cellulose, and are therefore considered to belong to t le vegetable kingdom, which multiply by simple division or fission, and are therefore called, after Naegeli, Schizomycetes (oxtfw, divide, and ,±vk^, ungus). Though they are considered as single-celled plants, their action is not quite m harmony with that generally attributed to plants, since, speaking m a general way, they do not possess in any conspicuous degree, like vegetable cells, the power of building up complex organic substances from simple inorganic material ; but, on the contrary, on the plan of animal cells they have in an eminent degree the character of destroying or breaking down ngher or complex organic molecules into those of simpler combinations, lhis is true m a general way, although, just as is the case with animal cells

exceptions are not wanting, i.e. instances when by synthetic processes the ■reverse takes place.

General Morphology

We will first consider the general morphological characters of bacteria. Bacteria are single cells of extremely minute size, 0-1 to 1/x 1 or more consistmg of a protoplasmic body-mycoprotein of Nencki, and an investing sheath of cellulose. The protoplasm while active and living is homogeneous when dead often appears granular ; it has great affinity for neutral and basic amhne dyes and m this respect compares with the substance of nuclei in vegetable and animal cells. There is no evidence of the presence in their protoplasm of any differentiation comparable to the nucleus in the animal or vegetable cell, although in some individual cases such a structure has been mentioned but this, owing to the methods of complex staining used for its demonstration, is not free from objection ; in the fresh state, and after the usual methods of staining, no differentiation of a nucleus can be recognised in the active and living cells constituting the elements of any bacterial species le protoplasm does, however, show m certain conditions and in certain species differentiation of denser and less dense parts, causing a segregation of the protoplasm into granules or particles ; this occurs in conditions generally taken m ica mg degeneration, but in several instances, to be mentioned later is

;“r bf°ng?ng to the llfe of the bacteria. Similarly, the appearance d dioplets m the protoplasm— vacuoles— can be noticed in certain

1 1 M =one micromillimetre = one twenty-five thousandth of an inch.

conditions. In some organisms granules of a special chemical nature have been noticed in the protoplasm (Cohn). The process of yacuolation is constantly noticed in conditions of fairly rapid multiplication ; the bacterial element elongates more or less, generally in the middle of 1 s pio op asl vacuole appears, and hereby the protoplasm segregates into two polar masses Such forms are very numerously met within all species of bacilli, and under the most varied conditions of growth and multiplication , o ten esevac have been, and still are, occasionally mistaken for spores (we beiow). liie cellulose sheath invests closely the protoplasm ; when le ce s e& the protoplasm breaks down and disappears, anc ie siea i

empty; during this process the sheath as a whole swells up into .a jelly, faintly granular, and gradually loses altogether its outlines. In many species of bacteria during rapid multiplication the sheath gives rise to a gelatinous secretion surrounding the . individuals, m fact forming ;a! kind ot general matrix — hyaline, viscous, and more or less am y lanu a new brood, and by this matrix a larger or smaller number o f the ™ remain aggregated together : it is not quite clear whether this mati derived from a gelatinous metamorphosis of the old sheaths, °r whettmi t a secretion or new formation by the new elements When, m an individu ^ the protoplasm divides into two masses, each of the new offs] pimgs i o - * its own investment, so that the old sheath, s we mg up in 8 afte‘, mass, persists as a sort of binding matrix ; m all those species ’

continued division, new elements remain aggregated together as group, Izoogltea, staphylococcus), the gelatinous matrix has this origin (Cohn), other cases the bacteria become invested outside the she at } a ge a

secretion which as a narrower or broader hyalme-lookmg zone invests the elements like a capsule, e.g. ascococcus Billrothi bacillus

pneumonia of Friedlander, and other capsulated cocci and bacilli of the same tribe In these instances of ‘ capsulated ’ bacteria the capsules are probablj special secretions and not the old swollen-up sheaths, since these capsule are wanting under certain different conditions of soil, while they are present and well marked in other conditions, the rapidity of multiplication having no influence whatever on the presence or absence of these capsules. These h valine capsules around the sheath must not be confounded with the swollen-up gelatinous sheath of bacteria in certain phases of their life, notably m e

degenerative^p ^ ^ protoplasm towards certain aniline dyes is greater

than that of the sheath, and that of the latter greater than of the matrix and capsules above mentioned, so that on staining with an aniline dye, t e protoplasm takes pp the dye quicker and more intensely than he sheath or the matrix ; and on withdrawing the dye, by washing m alcohol, or water, acid o“ alkalies or other special methods (see below), the protoplasm retains •Up ’ est" the capsules and matrix least. For this reason it will be found that by either of these ways it is possible to bring out these tin ee di e skuctures as different tints of the same dye, and further, that, owing to the rapidity with which the matrix and capsules can be depmed of the dye a second^e can be applied, to be taken up by them while the protoplasm and sheath have still retained the first dye. By these means various double and even treble, stainings can be effected by successive applications of different dyes. Acids and alkalies, chloroform, and alcohol, though affecting the fresh protoplasm, have no visible effect on the sheath and bactena acted upon by these reagents remain, therefore, unaltered both as to shape and aspect , anc these chemical reactions are often resorted to for the sake of differentiating bacteria — notably the spherical species-from similar forms of organic mattei not of bacterial nature. This is particularly important in the examination of animal tissues in the fresh state, in which tissue granules and rod-like forms, fat granules, &c., may easily give semblance to the presence of bacteria, but the test of acids and alkalies soon brings clearness into the matter. Other tests to be presently described, such as staining and cultivation, are of importance, and add certainty to the diagnosis.

Size op Bacteeia

The different species of bacteria differ one from another very considerably in size. Although all are of microscopical size, yet, comparing the different families and the different species in one family, sufficient differences will be detected to enable us to consider them as characteristic. The smallest bacteria are some of those species which, owing to their spherical form, are called cocci or micrococci.1 But also amongst the micrococci some are of considerable diameter, 1 /x or even more ; in the majority the individuals are considerably less, 0-5, 04, and even as small as Ol /x. But, as will be presently mentioned of other species, so also amongst the cocci of the same species, there occur the greatest differences in size under various conditions and in the various phases of growth. In an active state of growth, differences amounting to two and three and more times in size are noticed amongst the individuals of the same species in almost all media, sometimes less in fluid than in solid media ; for though the great majority of the individuals have the same size, there are always some that are much larger. The writer has specimens of various species of micrococci, notably those capable of forming chains or chaplets when growing in fluid media (streptococci), in which some of the cocci are several times the diameter of the smallest individuals ( see fig. 1). These large cocci can be shown to divide into medium-sized cocci, and these again into the small normal individuals.

Those forms of bacteria which, owing to their being more or less rod-shaped, are known by the name of bacilli show a diameter greater in length than in thickness. And in the size of both the thickness and length, different species vary very considerably. But it is chiefly the diameter in thickness which is for diagnostic purposes of greater importance than that in length. It must be understood that where in a given species, growing in a particular medium, the great majority of the individuals possess a certain length, this will be taken as the typical length, and is quite sufficient to serve for diagnostic purposes ; but in all species of bacilli, according to the phase of growth of the individuals, the length of the rods is subject to very great variations. In characterising the length of these individuals, it is therefore necessary to give the length of the shortest and the longest individuals. But whatever the length of the different individuals, their thickness is almost uniform, and therefore this would be of greater importance than the length. As a matter of fact, in not a few species of bacteria, with which we shall become acquainted in the course of this work, the individuals often vary between slight ovals of 0-5 /x in length, and long cylinders of 5 /x or more, and it would therefore not be quite correct to say that the average length of the cylindrical cells is about 3 to 4 ix, though there may be in a particular species numerous individuals of that length ; but notwithstanding these gross differences in the length of the cells, the thickness is uniform, though a few noteworthy exceptions are also here noticeable, as will bo mentioned later on.

1 The name 1 micrococci ’ was first applied by Hallier to the granules contained in some of his ‘ spores,’ which granules becoming free after bursting of the ‘ spores ’ germinate into various forms of microphytes. K okkos means a kernel.

Another important point, apart from the variations due to phase of growth, is the influence on size of the medium in which the bacteria are gi owing. This is in many instances considerable. One of the best cases is that of the bacillus anthracis, though many other species (micrococci and bacilli) behave in a similar manner. Bacilli of anthrax taken from the blood of an animal dead from virulent anthrax are a little more than half the thickness of the bacilli grown in neutral broth or neutral gelatine ; the majority of the rods of the former are in suitably prepared specimens made up of short, almost cubical ■cells, while of the latter the majority of the rods are distinctly cylindrical. But also the bacilli of anthrax derived from different species of animals dead of anthrax show differences in thickness and length. The same can be said ()f other bacilli (bacillus of typhoid fever, of swine fever, of tubercle, choleia, and others), both as regards length and thickness when growing in different media.

From all these considerations it follows that by naming a certain size as characteristic of the individuals of a species it is necessary to name also the source from, or the medium in which, they have been growing, and the phase of growth or length of time they have been growing, and, further, in the case of bacilli, to give the length of the shortest as well as the longest single individuals, or when the great majority are of a uniform size to state this as the typical length.

Shape of Bacteria

The first scientific classification of bacteria based on difference in shape was given by F. Cohn, and has been and still is, regarded as the most practical one, although within recent years it has undergone some not unimportant modifications. Cohn divided bacteria according to shape into : (a) spherical or micrococci ; ( b ) oval or bacterium proper, length only twice the thickness ; (c) cylindrical or bacilli, length more than twice the thickness ; (cl) curved or vibrio, and ( e ) spiral or spirilla, to which may be added the folded and long spirals or spirochete. Recent research has shown that the second division — i.e. the oval species of bacterium proper cannot stand as a separate species or rather group of species, since more accurate observation has shown that also amongst these some of the individuals attain the cylindrical shape. This group is therefore merged into the bacilli. Likewise, it has been shown that group (cl) cannot be separated from group (e), since the individuals of the species of group (cl) in continued growth attain the shape of spirals, and vice versa, that some of the spirillar forms are made up of individuals comparable to those of group (d). And lastly, the spirochetae cannot stand as a separate group and must be merged with those of the spirilla. So that at present, according to shape, only three groups can be correctly distinguished, viz. (1). cocci ; (2) bacilli ; and (3) spirilla ; the first comprises those species in which no matter what the phase or the medium is, the individuals are spherical or nearly spherical ; to the second group belong all those species in which the individuals may attain the rod or cylindrical shape ; and in the third the individuals are curved and may form spirals.

1. The Cocci.— A species in which the individuals are never cylindrical or rod-shaped cells, but are always more or less spherical, is called a micrococcus. But there are considerable differences amongst these and also amongst the individuals of the same species ; for in almost all these species there are phases of growth, in which the majority of individuals are not exactly spherical, but are either crescentic or dumb-bell-shaped — diplococci.1

1 SiTrAoOs, double.

Both these represent a phase in the division of the individuals ; and here again the daughter cells may be in immediate contact or may be already well separated one from another, according to whether they are in the act of dividing or already divided ; in the latter case, as much matrix will be found separating the new offsprings as in those that have completely divided : in this last case the individuals have the same spherical shape. In fig. 2, numerous dumb-bell forms are shown, in which the cocci are spherical ; in fig. 1, dumb-bells are seen in which the cocci are crescentic; and in fig. 5, single cocci are shown, all of uniform spherical form.

Careful examination has proved that some species which in former years were considered as belonging to the group ot micrococci are really bacilli, since under certain conditions of growth and, in certain phases, there are oval and even cylindrical individuals to be found amongst them, e.g. the pink organism, formerly spoken of as Micrococcus prodigiosus , has been shown to be really a bacillus ; the organism, held by Friedlander and others to be one of the organism of croupous pneumonia, and called the pneumococcus, is really a bacillus, called now the bacillus of Friedhinder, and many other species which at first sight appear in certain preparations to be cocci, and cocci only, but under other conditions of growth are shown to be bacilli ; e.g. the organism which is shown in fig. 8 and which is the organism of grouse disease. This microbe appears in the grouse as cocci and diplococci, many spherical, some also oval, few rod-shaped ; but numerous cylindrical forms exist in certain artificial cultures (broth) and in guineapigs and mice, inoculated with them.

A special form of cocci is represented by sarcina. Under this name are understood those species of micrococci which, owing to a rapid and repeated subdivision of the cocci in vertical lines, form groups of four cocci and multiples thereof. When a coccus divides into a dumb-bell or diplococcus, and each of these again divides in a direction vertical to the previous one, a group of 4 cocci is formed — Micrococcus tetragonus (fig. 4). In these groups each two cocci are crescentic with one more or less straightened side, or they are even square cut ; by further division of each coccus, the group increases from 4 to 8, 16, 32, and more ; but in these the cocci are always more or less subgrouped in fours — Sarcina lutea (fig. 3). Now, some species of cocci show under certain conditions of growth this tetragonal arrangement or grouping in fours in a conspicuous manner, others show it only imperfectly ; but even those that show it conspicuously under certain conditions show it less or in a not at all pronounced degree under other conditions of growth.

When owing to repeated division the cocci remain aggregated in larger or smaller groups, which themselves gradually extend as reproduction proceeds, and are connected by streaks of cocci in a more or less irregular fashion, such cocci are called staphylococci ( staphylis , a bunch of grapes), to distinguish them from a species of cocci which, after division, remain joined in a linear series. By this latter method of division chaplets or chains of cocci are formed which, according to the number of subdivisions, are shorter or longer ; such a chain-forming coccus is called streptococcus (streptos, bent, twisted), because generally these chains, particularly when long, are more or less wavy and twisted. In these chains the cocci are often arranged as dumb-bells, this indicating the actual phase of division or one immediately after ; in others, the cocci are of equal distance, indicating the phase before division of the individual cocci has commenced. Always, however, one meets with individual cocci in chains which are considerably larger than the rest ; these are found either in the chain or, more commonly, at one end; in the latter case they are sometimes club- or pear-shaped. Whether these larger cells represent a particularly active element or one that has undergone involution, is not easily to be made out. From what will be stated below of similar forms of bacilli, the writer is inclined to think that they are not involution forms, but indicate an altogether different phase, viz. atavism or a reversion to an antecedent form in the history of the evolution of the cocci.

2. The Bacilli. — All bacilli are rod-shaped or cylindrical cells, which differ one from another in the length and thickness of the cells. In the same species, as mentioned above, there occur the greatest differences as regards the length of the rods. While in a good many species, to be hereafter more minutely described, even the shortest or youngest elements are distinctly cylindrical, there are numerous species in which the youngest elements do not differ from spherical or crescentic cocci ; these are then chiefly arranged as diplococci and represent a rapid mode of division of young elements ; but there are present already in early stages elements which are distinctly cylindrical, and, as growth proceeds, these cylindrical elements increase in number and in length. W e could name here a long series of species of pathogenic bacilli, which, when taken from the blood of an animal, or growing on gelatine or agar mixture, show in the earlier stages the majority of the elements as oval rods ; some, like dumb-bells, constricted in the middle; but in broth cultures there are also noticeable numerous cylindrical elements in the early stages. After a few days’ growth on solid media (gelatine, agar) numerous cylindrical elements are met with. Thus, the microbes known as connected with, and causing rabbits’ and pigeons’ septicaemia of Davaine and Koch, the organism of swine fever and of Wildseuche, of infectious fowl enteritis, of guinea-pigs’ septicaemia, of fowl cholera, of the Middlesbrough (human) pneumonia, of grouse disease, the bacillus of Friedlander and several species allied to this, the bacillus pyocyaneus, the bacillus of veal and pork pie, and others when taken from the blood or tissues, or from early cultures on solid media (gelatine or agar mixture) — all these are like diplococci or slightly oval organisms ; when examined, after a few days’ growth on these media, they are in numerous individuals cylindrical, some four or five times longer than they are thick.

All these species taken from early cultures on gelatine or agar mixture, or from the blood and tissues, would in former years have been regarded as belonging to Cohn’s group of bacteria proper. But also in species, about whose bacillary nature there never was any question, some individuals occur in all cultivations which do not differ from cocci and diplococci, being spherical or slightly oval cells, singly, or more commonly as dumb-bells ; such is the case with the tubercle bacillus, with the bacillus of diphtheria, and with a variety of species of non-patliogenic bacilli. But here the question whether or not they are bacilli is at once answered by the occurrence in the same preparations of numerous, or even the majority of, cylindrical elements.

Now, the opinion has been repeatedly expressed by various observers (Naegeli, Lankester, Zopf, and others) that there exists no well-marked boundary between the different forms separated by Cohn as micrococci, as bacilli, and as spirilla, on account of the transitional forms between each of the two groups. As we have shown above, numerous species of bacilli exist, in each of which cocci, cylindrical forms and intermediate forms, do occur ; but does this justify us in saying that between the species of micrococci and those of bacilli, intermediate species occur, and that there is no definite boundary between them ? Clearly not. In those species that are micrococci,.

the elements, under every condition of growth that has been tried, always appear as cocci, either singly or as diplococci, as staphylococci or as streptococci, as the case may be, and never as cylindrical rods : these are clearly and decidedly species of micrococci. In some of the species oi bacilli, on the other hand, the youngest forms may not be larger than a spherical or cubical mass of protoplasm, may therefore not differ morphologically from a coccus, but have the power to elongate into rod- or cylindrical-shaped cells ; in other species, again, even the youngest elements are as a rule, cylindrical, although also here amongst these well-pronounced bacillary forms under certain conditions some elements appear almost spherical or cubical, e.g. bacillus anthracis, bacillus of tubercle, bacillus of diphtheria, as will be shown later on ; and the same holds good also for some of the species which are spirilla, for, as we shall presently show, the youngest forms also of these appear as mere spherical or oval masses of protoplasm, capable of elongating into more or less curved rods and cylinders, and these by continued growth elongate into wavy or spirally twisted chains or threads. But because in a certain state they are like cocci, we shall not put them down as micrococci, and because between the cocci forms and the spirillar forms intermediate shapes occur, we shall not consider them as indicating a change of species, as if micrococci were to change into spirilla ; but since in their adult phase they grow into spirilla, we shall call such species spirilla.

An organism has been minutely described by Zopf as Cladotlirix dichotoma: in this organism there is no doubt that cocci, straight rods, isolated and in chains, and shorter or longer spirilla do occur, but it is not at all permissible to consider this as evidence that between the three groups of bacteria, viz. micrococci, bacilli, and spirilla, there is no definite boundary line. The cocci-form of the Cladotlirix dichotoma when sown on the different media will again give rise to Cladotlirix dicliotoma, and will never become or grow as micrococci ; and if the bacillary forms of this microbe are watched in their growth, it will be seen that some of them again give rise to spirilla. This same phenomenon can be easily ascertained in some of the typical spirillar species, e.g. the spirillum of Finlder, of Koch, the spirillum of noma. In all cultures, after a few days’ growth, forms show themselves which do not differ from cylindrical bacilli, in which a curve of the rods is very slightly or not at all indicated ; they appear as single rods, as dumb-bell rods, or as slightly wavy chains or threads, yet on further growth they are capable of becoming curved and assuming the spirillar form.